Obesity is a common problem. Simply stated, obesity is an excess accumulation of adipose tissue which contains fat stored in the form of triglycerides. The number of cells in the body is determined at least by late adolescence and while the number of adipocyte cells may increase, it does not decrease. Thus, weight gain can result from an enlargement of adipocyte cells or an increase in their number. Typically, obese individuals have hypertrophic cells and the severely obese have an increase in adipose cell number as well as hypertrophy. An obese patient only reduces the fat in his cells when he loses weight. Further, he may not ever lose the tendency to gain weight.
Body weight is regulated by an endogenous body mechanism. Physiological and neurological properties establish and maintain a given weight. Briefly stated, glycerol which is released during hydrolysis of triglycerides and adipose tissue is widely believed to regulate caloric intake and metabolism. Others have postulated that caloric intake is affected by both body temperature and environmental temperature. In addition, cell size and number affect energy regulation. Weight gain cannot be predicted solely on the amount of calories ingested.
In normal persons, thermogenesis is an adaptive mechanism which increases the metabolic rate after overeating. While a normal person will experience an increase in thermogenesis following increased caloric intake, the obese either has a substantially decreased thermogenic mechanism or lacks this particular mechanism entirely.
The use of dinitrophenol to treat obesity is known. Dinitrophenol is known to elevate the body temperature and produces a marked increase in caloric metabolism. However, ingestion of massive amounts of dinitrophenol causes toxicity by the uncoupling of oxidative phosphorylation in the mitochondria of cells. Because of this toxicity, excessive amounts can result in profuse diaphoresis, fever, thirst, tachycardia and respiratory distress which can lead to hyperpyrexia, profound weight loss, respiratory failure and death. The minimum fatal human oral dose is estimated at one to three grams (approximately 20-30 mg/kg).
In methods heretofore known to using dinitrophenol to induce weight loss, while initial daily dosages have usually been much less than the toxic amount, about 100-250 mg, as the treatment progressed the patient normally developed a tolerance for dinitrophenol and the dosage was increased to obtain the same results. This increased dosage led to an increased frequency of toxic symptoms and general disuse of dinitrophenol in inducing weight loss.
It has also been known to use drugs with thyroid hormone activity for the treatment of obesity. However, as described in Physicians' Desk Reference, Medical Economics Co. Inc., (Oradell, N.J.), 37th Ed. (1983), in euthyroid patients, it is well established that doses within the daily hormonal requirements are ineffective for weight reduction. However, larger doses may produce serious or even life-threatening manifestations of toxicity.